Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance.

BACKGROUND: Working memory (WM) deficits in schizophrenia have been associated with dorsolateral prefrontal cortex (DLPFC) dysfunction in neuroimaging studies. We previously found increased DLPFC activation in schizophrenic versus normal subjects during WM performance (Manoach et al 1999b). We now have investigated whether schizophrenic subjects recruit different brain regions, particularly the basal ganglia and thalamus, components of frontostriatal circuitry thought to mediate WM. METHODS: We examined regional brain activation in nine normal and nine schizophrenic subjects during WM performance using functional magnetic resonance imaging. Subjects performed a modified version of the Sternberg Item Recognition Paradigm that included a monetary reward for correct responses. We compared high and low WM load conditions to each other and to a non-WM baseline condition. We examined activation in both individual subjects and averaged group data. RESULTS: Relative to normal subjects, schizophrenic subjects exhibited deficient WM performance, at least an equal magnitude of right DLPFC activation, significantly greater left DLPFC activation, and increased spatial heterogeneity of DLPFC activation. Furthermore, only the schizophrenic group activated the basal ganglia and thalamus, even when matched for task performance with the normal group. CONCLUSIONS: Aberrant WM performance and brain activation in schizophrenia may reflect dysfunction of frontostriatal circuitry that subserves WM. Future studies will elucidate the contribution of the anatomical components of this circuitry to WM deficits.

Rehabilitating effect of vitamin E therapy on the ultrastructural changes in skeletal muscles of vitamin E-deficient rabbits.

Ultrastructural repair of the morphological damages produced in nutritional muscular dystrophy was studied by refeeding dystrophic rabbits with vitamin E. Weanling (1.2 kg body weight) rabbits were fed a vitamin E-deficient diet for 24 days. Half of this group was then sacrificed and the remainder was given an initial oral dose of 50 mg of DL-alpha-tocopherol acetate and a vitamin E supplemented diet for 28 days. Control animals were fed a vitamin E supplemented diet with 50 mg of DL-alpha-tocopherol acetate per kilogram of diet. Abnormalities of dystrophic muscles included streaming Z-disk, degenerated mitochondria, fragmented sacroplasmic reticulum and development and aggregation of myelin figures. The effect of vitamin E therapy resulted in significant repair of the dystrophic muscle. Small localized sections of rehabilitated muscle revealed abnormal mitochondria and residual myelin figures.